title: Stearylated antimicrobial peptide melittin and its retro isomer for efficient gene transfection.
abstract: A crucial bottleneck in nonviral vector-mediated gene delivery is poor endosomal escape. Here, we constructed novel gene vectors by coupling the stearyl moiety to the N-terminus of the antimicrobial peptide melittin (stearyl-Mel) and its retro isomer (stearyl-rMel) due to their high membrane-lytic activity. As expected, stearyl-Mel showed obvious increases in endosome-lytic activity and transfection efficiency compared with the reported stearyl-TP10. More gratifyingly, the transfection efficiency of stearyl-rMel was around 10-fold greater than that of stearyl-Mel and almost reached the transfection levels of Lipofectamine 2000 due to the enhanced endosome-lytic activity. Furthermore, the stearyl-rMel/p53 plasmid complex exhibited higher p53 expression and antitumor activity than stearyl-Mel, confirming the fact that stearyl-rMel displayed higher transfection efficiency. Taken together, the combination of the stearyl moiety with retro melittin provides a novel framework for the development of excellent nonviral gene vectors.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology, School of Life Sciences, , Lanzhou University , Lanzhou 730000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.forename: Ranran
authors.initials: R
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.forename: Guolin
authors.initials: G
authors.lastname: Li
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Yan
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016466:CHO Cells; D019556:COS Cells; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008555:Melitten / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015394:Molecular Structure; D013229:Stearic Acids / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D013229:Stearic Acids; D008555:Melitten; C031183:stearic acid